1. Field of the Invention
The present invention relates generally to implantable defibrillator systems, and more particularly, to a method and apparatus for generating biphasic waveforms with an implantable defibrillator system.
2. Background of the Invention
Implantable defibrillator systems deliver a high voltage electrical countershock to the heart in an attempt to correct or convert a detected cardiac arrhythmia or fibrillation. Due to the limitations on size and power imposed by the fact that these systems must be self-contained implantable devices, all existing implantable defibrillator systems generate an electrical countershock by charging a capacitor system to a high voltage. The electrical charge stored in the capacitor system is then delivered as a truncated capacitive discharge through two or more implanted electrodes.
To date, there have been two basic kinds of truncated capacitive discharge waveforms which have been used with implantable defibrillator systems: monophasic waveforms and biphasic waveforms. Monophasic waveforms are comprised of a single monotonically decaying electrical pulse that is typically truncated before the capacitor system is completely discharged. Biphasic waveforms, on the other hand, are comprised of a pair of decaying electrical pulses or phases that are of opposite polarity. To generate a biphasic pulse, a first pulse or phase is discharged from the capacitor system in the same manner as a monophasic waveform and then, at the point the first pulse is truncated, an H-bridge switch circuit connected to the electrodes is used to immediately reverse the discharge polarity of the capacitor system as seen by the electrodes in order to produce the second pulse or phase of the biphasic waveform that is of the opposite polarity. A typical example of the use of an H-bridge circuit to generate a biphasic waveform in an implantable defibrillator system is shown in U.S. Pat. No. 4,998,531.
Over the last twenty five years, it has been demonstrated that appropriately truncated biphasic waveforms can achieve defibrillation with significantly lower currents, voltages and energies than monophasic waveforms of similar durations. Kroll, MW et al., "Decline in Defibrillation Thresholds", PACE 1993; 16#1:213-217; Bardy, GH et al., "A Prospective Randomized Evaluation of Biphasic vs. Monophasic Waveform Pulses on Defibrillation Efficiency in Humans", J American College of Cardiology, 1989; 14:728-733; and Wyse, DG et al., "Comparison of Biphasic and Monophasic Shocks for Defibrillation using a Non-Thoracotomy System", American J Cardiology 1993; 71:197-202. These findings are of particular importance for implantable devices because of the direct relationship between the amount of energy required for defibrillation and the overall size of the implantable device, i.e., the lower the energy required for defibrillation, the smaller the device.
Numerous theories have been advanced to explain the improved efficiency of the biphasic waveform over the more conventional monophasic waveform. Several of these theories may be relevant and may in fact act jointly. To date, the following general theories have been advanced in the literature: (1) zero net charge transfer; (2) current summing; (3) sodium channel reactivation; (4) shortening of the refractory period; (5) lowering of the impedance; (6) improved energy delivery; and (7) change in the critical point. As a background, each of these theories will be briefly summarized to contrast them with the theory employed by the present invention.
(1) Zero Net Charge Transfer--The first paper on the biphasic defibrillation waveform was arguably presented by Schuder in 1964. In that paper he observed, "an important feature of the one-cycle bi-directional shock is that, despite the arbitrary starting point, the net electrical charge transport is zero." Schuder JC, Stoeckle EH, Dolan AM, "Transthoracic Ventricular Defibrillation with Square-Wave Stimuli: One-Half Cycle, One Cycle, and MultiCycle Waveforms", Circulation Research 1964;15:258-264. However, a recent study found a negative correlation between the charge contents in each phase of efficient biphasic shocks of a certain design. Walker RG, Walcott GP, Swanson DK, et.al., "Relationship of Charge Distribution between Phases in Biphasic Waveforms", Circulation 1992;86 No.4:I-792. (Abstract). This would imply that a zero net charge transfer was not required or necessarily efficient, and that a zero net charge transfer (at least at the electrode level) may not be important for the efficacy of a biphasic waveform.
(2) Current Summing--It has also been suggested that when the second phase of a biphasic pulse is removed, thereby creating a monophasic pulse, it is necessary to increase the discharge voltage of this pulse so that the current amplitude would be equal to the sum of current values of 2 first half periods for the discharge. Consequently, the capacity of the heart to summate the stimulation effect of both phases of current may be utilized for reduction of the defibrillating current in one direction and for decreasing the hazard of the heart injury by a strong current. Gurvish NL, Markarychev, VA: "Defibrillation of the Heart with Biphasic Electrical Impulses", Kardiologilia 1967;7:109-112. A similar result was found more recently suggesting that the total voltage change from the trailing edge of the first phase to the leading edge of the second phase was an important factor in the defibrillation pulse. Tchou P, Krum D, Aktar M, Avitall B, "Reduction of Defibrillation Energy Requirements with new Biphasic Waveforms", PACE 1990; 13:507. (Abstract) The summing hypothesis is tempting in that the sum of the currents (or voltages) in the two phases of a biphasic shock is indeed comparable to the current in a monophasic shock of similar efficacy. However, this theory does not explain the sensitivity of the biphasic efficiency to the duration of the second phase.
(3) Reactivation of the Sodium Channels--It has been suggested that the first phase of the biphasic waveform serves as a conditioning prepulse which helps to restore sodium channel activation in preparation for the excitation by the second phase. Jones JL, Jones RE, Balasky G, "Improved Cardiac Cell Excitation with Symmetrical Biphasic Defibrillator Waveforms", American J Physiology 1987;253:H1418-H1424. This reactivation hypothesis was given additional support and a theoretical underpinning in a later paper which demonstrated that a hyperpolarizing prepulse did reactivate additional sodium channels thus promoting increased excitability. Kavanagh KM, Duff HJ, Clark R, et.al., "Monophasic vs. Biphasic Cardiac Stimulation: Mechanism of Decreased Energy Requirements", PACE 1990:13;1268-1276. This theory may explain why the biphasic wave prolong refractoriness after the shock. Swartz JF, Jones JL, Jones RE, Fletcher RD, "Conditioning Prepulse of Biphasic Defibrillator Waveforms Enhances Refractoriness to Fibrillation Wavefronts", Circulation Research 1991;68:438-449. Unfortunately, this enhanced stimulation effect is very dependent on waveform duration. Karasik P, Jones R, Jones J., "Effect of Waveform Duration on Refractory Period Extension Produced by Monophasic and Biphasic Defibrillator Waveforms", PACE 1991;14:715. (Abstract). Thus, the reactivation theory for biphasic waveforms may or may not be important depending upon the importance of the extension of refractory period vs. synchronization as the fundamental basis of defibrillation.
(4) First Phase Shortening of Refractory Period--It has been long known that a hyperpolarizing pulse delivered during phase 2 of the action potential can shorten the refractory period, thus, allowing a depolarizing pulse to more easily activate the cell, and it has been suggested that this mechanism could explain the increased effectiveness of the biphasic shock. Tang ASL, Yabe S, Wharton JM, et.al., "Ventricular Defibrillation Using Biphasic Waveforms: The Importance of Phasic Defibrillation", J American College of Cardiology 1989;13:207-14. This proposed theory is similar to the sodium channel reactivation hypothesis and the cited literature may apply in both cases.
(5) Lower Impedance--There is some evidence that the average current of a pulse is the best measure of its effectiveness (for a given pulse duration). Bourland JD, Tacker WA, Geddes LA. et al., "Comparative Efficacy of Damped Sign Wave and Square Wave Current for Transchest Ventricular Defibrillation in Animals", Medical Instrumentation 1978;12#1:38-41. Thus, for a given voltage in a waveform, one would expect that the waveform with the lowest impedance would be the most efficacious. It has been found that the average impedance of the second phase of a biphasic waveform is significantly lower than that of the first phase. Tang ASL, Yabe S, Wharton JM, et.al., "Ventricular Defibrillation Using Biphasic Waveforms: The Importance of Phasic Defibrillation", J American College of Cardiology 1989;13:207-14. The lower impedance theory, however, is suspect for two reasons. First, the reductions in required voltage are found to be lower than the impedance reductions and, as a result, the current requirement is itself reduced for the biphasic waveform. Second, the impedance reduction results from the transition between the phases and thus only benefits the second phase of the shock. As a result, the lower impedance theory does not explain the overall improvements in efficacy which have been observed for the biphasic waveform.
(6) Improved Energy Delivery--It has been suggested that the increased efficacy of the biphasic waveform is due to its ability to deliver a larger fraction of the energy in the capacitor for a typical capacitive discharge defibrillator. U.S. Pat. No. 4,850,357, issued to Bach and entitled "Biphasic Pulse Generator for an Implantable Defibrillator". Clearly one could deliver more of the energy in a capacitor by merely increasing the duration of the pulse, but this has been shown to be deleterious in that long durations can lower the average current and thereby decrease efficiency. Kroll MW, Adams TP, "The Optimum Pulse Width for the Implantable Defibrillator", 7th Purdue Conference on Defibrillation, American Heart Journal 1992;124#3: 835. (Abstract).
For general stimulation and defibrillation, it has been shown that pulses significantly wider than the appropriate chronaxie time use energy inefficiently. Irnich W, "The Chronaxie Time and its Practical Importance", PACE 1980;8:870-888. By delivering the energy in two shorter phases, one could utilize the energy without the penalty of the increased duration. A reasonably efficient capacitive discharge monophasic waveform will deliver nearly 90% of the capacitor's energy with an efficient pulse duration. By use of the biphasic waveform one can thus deliver another 10% of the energy. However the energy reductions reported, for biphasic usage, are significantly greater than 10%. It has also been shown that, for a more optimal duration, the stored energy requirements were also lowered with the biphasic waveform. Swartz JF, Karasik PE, Donofrio J, et.al., "Effect of Biphasic Waveform Tilt on Human Non-Thoracotomy Defibrillation Threshold", PACE 1993;16#4II:888 (Abstract). Thus, the argument that the increased benefit of biphasic waveforms might lie from increasing the percentage of energy delivered can certainly not account for all of the effects which have been observed.
(7) Differences in the Critical Point--It has been suggested that differences in the critical point of the biphasic waveform may explain its advantage over the monophasic waveform. Ideker RE, Tang ASL, Frazier DW, et.al., "Ventricular Defibrillation: Basic Concepts", Cardiac Pacing and Electrophysiology 3rd Ed., edited by El-Sherif N & Samatt, WB Saunders Co. Philadelphia 1991;42:713-726. Re-entry may be induced when a sufficient potential gradient exists that is at an angle (e.g., perpendicular) to the dispersion of refractoriness. This has been shown to exist with a shock field of 5 V/cm in tissue just recovering from its effective refractory period. Frazier DW, Wolf PD, Wharton JM, et.al., "A Stimulus Induced Critical Point: A Mechanism for Electrical Initiation of Re-Entry in Normal Canine Myocardium", J of Clinical Investigation 1989;83:1039. According to this theory, it is thought, because these potential gradients exceeding the critical value can cause unidirectional block and prolongation of refractoriness, there is a lower critical point. If the biphasic shock has a lower critical point, then there is less of a chance of refibrillation from the shock. It has been shown, however, that the first reactivation following an unsuccessful countershock is typically found in the region with the lowest gradient, not the highest. Shibata N, Chen PS, Dixon EG, et. al., "Epicardial Activation After Unsuccessful Defibrillation Shocks Dogs", American J Physiology 1988;255:H902-H909
Beside the experimental findings that the biphasic waveform has lower defibrillation thresholds, there are several specific findings which should be considered to better understand the nature of the difference between monophasic and biphasic waveforms. Most importantly, these experimental findings should be explainable by any putative theory of the biphasic waveform advantage. These specific findings are: (1) the biphasic wave generates fewer post shock arrhythmias; (2) a symmetric biphasic offers minimal or no benefit; (3) the second phase duration for a single capacitor shock should be shorter than the first duration; and (4) there is less benefit with the biphasic waveform for transthoracic defibrillation.
(1) Biphasic Waveform has Fewer Post Shock Arrhythmias--There are several reports that the biphasic waveform has fewer post shock arrhythmias than does the monophasic waveform for shocks of equal strength. This is certainly true for shocks near their threshold levels. This was first noted as a "distinct impression" without a statistical analysis in the early Schuder paper, and was confirmed in a recent study with dogs. Zhou X, Daubert JP, Wolf PD, et al., "Epicardial Mapping of Ventricular Defibrillation With Monophasic and Biphasic Shocks in Dogs", Circulation Research 1993;72:145-160. When the duration of the post shock arrhythmias is measured by detecting the contraction arrest time, it has been shown that the arrest time for rectangular biphasic waveforms with optimal durations could be reduced to half of the arrest time associated with monophasic waveforms of similar strength. Jones JL, Jones RE. Decreased Defibrillator--Induced Dysfunction with Biphasic Rectangular Waveforms. American J Physiology 1984;247:H792-H796.
(2) Symmetric Biphasic Offer Little or No Benefit--A study of isolated perfused canine hearts using symmetrical biphasic pulses--each phase had an identical amplitude and durations of 5 ms--showed no advantage in the threshold energy for defibrillation. Niebauer MJ, Babbs CF, Geddes LA, et.al., "Efficacy and Safety of the Reciprocal Pulse Defibrillator Current Waveform", Medical and Biological Engineering and Computing 1984;22:28-31. In this study, myocardial depression was defined as the percentage decrease in systolic pressure, and it was found that the symmetric biphasic waveform also offered no advantage in minimizing myocardial depression at any multiple of the defibrillation threshold current. Similar results were obtained with a "double capacitor" biphasic waveform in which a separate capacitor was used for each phase to ensure symmetry. Kavanagh KM, Tang ASL, Rollins DL, et.al., "Comparison of the Internal Defibrillation Thresholds for Monophasic and Double and Single Capacitor Biphasic Waveforms", J American College of Cardiology 1989;14:1343-1349. Another example that symmetric biphasic waveforms offer no advantage is a study that used a single capacitor waveform of 7 ms which had a threshold of 1.19 J, while the symmetric dual capacitor waveform with both the first and second phase each being 7 ms had a 1.99 J threshold. Feeser SA, Tang ASL, Kavanagh KM, et.al. Strength--Duration and Probability of Success Curves for Defibrillation with Biphasic Waveforms. Circulation 1990;82:2128-2141.
(3) Efficient Biphasic Has Phase 2 Shorter than Phase 1--In a study done with a right ventricular catheter and a subcutaneous patch in dogs, single capacitor biphasic waveforms for which the first phase was 50, 75, and 90% of the total duration had a lower defibrillation energy threshold than a monophasic waveform of the same total duration. However for waveforms in which the second phase had 75 or 90% of the total duration the energy requirements increased significantly. Chapman PD, Vetter JW, Souza JJ, et.al. "Comparative Efficacy of Monophasic and Biphasic Truncated Exponential Shocks for Nonthoracotomy Internal Defibrillation in Dogs. J American College of Cardiology 1988;12:739-745.
Similar results were found in dogs with epicardial patch electrodes in which a total of 25 combinations of first and second phase durations were studied. In all cases in which the second phase duration was shorter than the first phase duration, the total energy required was lower than that of a monophasic wave whose duration was equal to the first phase duration of the biphasic wave. Conversely, in all cases in which the second phase duration was greater than the first phase, the energy requirements were increased over the comparable monophasic waveform. Feeser SA, Tang ASL, Kavanagh KM, et.al., "Strength--Duration and Probability of Success Curves for Defibrillation with Biphasic Waveforms", Circulation 1990;82:2128-2141.
Still another canine study used both epicardial and pericardial patches found that the single capacitor biphasic waveforms with the lowest energy thresholds had a second phase shorter than the first phase. As with the other studies, those shocks with the second phase longer than the first phase had thresholds greater than that of comparable monophasic waveforms. Dixon EF, Tangas L, Wolf PD, Meador JT, Fine MG, Calfee RV, Ideker RE, "Improved Defibrillation Thresholds with Large Contoured Epicardial Electrodes and Biphasic Waveforms", Circulation, 1987;76:1176-1184.
(4) Biphasic Waveform Has Less Transthoracic Advantage--Another canine study compared monophasic and biphasic thresholds for both internal and external defibrillations. While the biphasic waveforms had energy thresholds that were approximately one half of those of the monophasic waveforms for internal defibrillation, the advantages of the biphasic waveform in external defibrillation, although still seen although, were usually not statistically significant when comparing waveforms of similar durations. Johnson EE, Hagler JA, Alferness CA, et al., "Efficacy of Monophasic and Biphasic Truncated Exponential Shocks for Nonthoracotomy Internal Defibrillation in Dogs", J American College of Cardiology, 1988;12:739-745.
Although some of these theories may partly explain, or may act cooperatively to explain, the various experimental effects which have been observed when a biphasic waveform is applied to the heart, there is currently no single accepted theory which fully explains the advantages of the biphasic waveform over the monophasic waveform. As a result, there is little or no agreement on what factors might further improve the efficiency and operation of the biphasic waveform.
This lack of agreement as to the theoretical basis for the enhanced efficacy and operation of the biphasic waveform has resulted in the use of two different techniques for generating and delivering biphasic waveforms from an implantable defibrillator. In the first technique, as described for example in U.S. Pat. No. 4,850,357 issued to Bach, Jr., each phase of the biphasic waveform is controlled by truncating the discharge of the capacitor system at a predefined tilt or percentage exponential decay as sensed by an output sensing circuit. This first technique for generating biphasic waveforms is used in the PRC.RTM. and Jewel.RTM. devices manufactured by Medtronic, Inc., as well in the PRx.RTM. and PRx II.RTM. devices manufactured by CPI, Inc. In the second technique, as described, for example in U.S. Pat. No. 4,821,723 issued to Baker et al., each phase of the biphasic waveform is controlled by truncating the discharge of the capacitor system at a predefined time interval as measured by some type of timer. This second technique for generating biphasic waveforms is used in the Cadence.RTM. device manufactured by Ventritex, Inc., as well as in the Guardian.RTM. device manufactured by Telectronics, Inc.
While existing implantable defibrillator systems are capable of generating electrical countershocks that utilize the more efficient biphasic waveform, there presently is no single accepted theory for why the biphasic waveform is more efficient. This lack of an understanding of the nature and effect of the biphasic waveform has impeded further development and enhancement of the biphasic waveform. Accordingly, it would be desirable to provide a method and apparatus for generating biphasic waveforms as a result of an improved understanding of the nature and effect of the biphasic waveform on the fibrillating myocardium.